Abstract
Sodium channel expression in inner ear afferents is essential for the transmission of vestibular and auditory information to the central nervous system. During development, however, there is also a transient expression of Na+ channels in vestibular and auditory hair cells. Using qPCR analysis, we describe the expression of four Na+ channel genes, SCN5A (Nav1.5), SCN8A (Nav1.6), SCN9A (Nav1.7), and SCN10A (Nav1.8) in the human fetal cristae ampullares, utricle, and base, middle, and apex of the cochlea. Our data show distinct patterns of Na+ channel gene expression with age and between these inner ear organs. In the utricle, there was a general trend toward fold-change increases in expression of SCN8A, SCN9A, and SCN10A with age, while the crista exhibited fold-change increases in SCN5A and SCN8A and fold-change decreases in SCN9A and SCN10A. Fold-change differences of each gene in the cochlea were more complex and likely related to distinct patterns of expression based on tonotopy. Generally, the relative expression of SCN genes in the cochlea was greater than that in utricle and cristae ampullares. We also recorded Na+ currents from developing human vestibular hair cells aged 10–11 weeks gestation (WG), 12–13 WG, and 14+ WG and found there is a decrease in the number of vestibular hair cells that exhibit Na+ currents with increasing gestational age. Na+ current properties and responses to the application of tetrodotoxin (TTX; 1 μM) in human fetal vestibular hair cells are consistent with those recorded in other species during embryonic and postnatal development. Both TTX-sensitive and TTX-resistant currents are present in human fetal vestibular hair cells. These results provide a timeline of sodium channel gene expression in inner ear neuroepithelium and the physiological characterization of Na+ currents in human fetal vestibular neuroepithelium. Understanding the normal developmental timeline of ion channel gene expression and when cells express functional ion channels is essential information for regenerative technologies.
Highlights
Voltage-gated sodium channels are essential for the propagation of action potentials in neurons
There is a diversity in the expression of Na+ channel genes including Nav 1.1–Nav 1.9 in the inner ear at different stages of development (Mechaly et al, 2005; Wooltorton et al, 2007; Fryatt et al, 2009; Frucht et al, 2011; Yoshimura et al, 2014; Liu et al, 2016), that is thought to be important for establishing appropriate neural connections
In inner hair cells (IHCs), during embryonic and early postnatal development, there is a transient expression of Na+ channels that are responsible for modulating spike frequency of Ca2+-evoked action potentials (Marcotti et al, 2003; Eckrich et al, 2012)
Summary
Voltage-gated sodium channels are essential for the propagation of action potentials in neurons. The β-subunits of voltage-gated Na+ channels, encoded by SCNB genes have been tracked in the developing the inner ear (Wooltorton et al, 2007; Liu et al, 2016) Complementing these molecular results are anatomical investigations that have documented the expression and location of various Na+ channel α-subunits within hair cells, afferent terminals, and ganglia of the auditory and vestibular systems (Wooltorton et al, 2007; Lysakowski et al, 2011; Eckrich et al, 2012; Kim and Rutherford et al, 2016; Liu et al, 2016; Zhou et al, 2020). With the onset of hearing (after PND 12 in mice), there is a down-regulation of these Na+ channels in IHCs
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